DOCSLIB.ORG

How We Feel: Ion Channel Partnerships That Detect Mechanical Inputs and Give Rise to Touch and Pain Perception

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
How We Feel: Ion Channel Partnerships That Detect Mechanical Inputs and Give Rise to Touch and Pain Perception Neuron Review How We Feel: Ion Channel Partnerships that Detect Mechanical Inputs and Give Rise to Touch and Pain Perception Shana L. Geffeney1,2 and Miriam B. Goodman1,* 1Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA 2Present address: Department of Biology, Utah State University-Uintah Basin, 320 N. 2000 W. (Aggie Boulevard), Vernal, UT 84078, USA *Correspondence: [email protected] DOI 10.1016/j.neuron.2012.04.023 Every moment of every day, our skin and its embedded sensory neurons are bombarded with mechanical cues that we experience as pleasant or painful. Knowing the difference between innocuous and noxious mechanical stimuli is critical for survival and relies on the function of mechanoreceptor neurons that vary in their size, shape, and sensitivity. Their function is poorly understood at the molecular level. This review emphasizes the importance of integrating analysis at the molecular and cellular levels and focuses on the discovery of ion channel proteins coexpressed in the mechanoreceptors of worms, flies, and mice. Introduction activate or inhibit mechanoreceptor neurons can exert their influ- All sensory neurons are alike. Each detects a physical stimulus ence by acting on channels other than transduction channels. For and produces an electrical signal that gives rise to behavioral example, naked mole rats are insensitive to the persistent skin responses, conscious perceptions, or both. Many operate near acidification that is a feature of their environment. These animals the physical limits of detection and operate over a dynamic range have acid-gated ion channels (ASICs) with a similar sensitivity to of several orders of magnitude (Bialek, 1987; Block, 1992). These protons (H+) as those found in mice. However, the voltage-gated properties suggest that they are endowed with a detector, an Na+ channels expressed in their C-fiber nociceptors are hyper- amplifier, and mechanisms for gain control. One of the most sensitive to inhibition by protons and this inhibition counterbal- striking and well-understood examples is the ability of photore- ances the excitation due to ASIC activation, rendering animals ceptors to detect single photons while retaining sensitivity to light insensitive to acidification (Smith et al., 2011). Thus, the differ- intensities that vary by nine orders of magnitude (Rieke and ence in nociceptor sensitivity stems from variation in voltage- Rudd, 2009). gated Na+ sodium channels that are essential for action potential Each somatosensory neuron is distinct. The somatosensory generation rather than any variation in sensory transduction. system is a collection of neurons innervating the skin, muscle, Though mechanoreceptor neurons were first studied more joints, tendons, and internal organs that establish and maintain than 75 years ago (Adrian, 1926; Adrian and Zotterman, 1926a, sensitivity across a range of stimulus intensities and frequencies. 1926b), the events that link sensory stimulation to neuronal acti- This collection includes nociceptors that require stimulation vation are only beginning to be understood. Today, the protein above a high threshold for activation. Nociceptors are respon- partners responsible for detecting mechanical stimuli have sible for informing the brain about damage to peripheral tissues, been identified only for a few mechanoreceptor neurons in the an essential function that enables the nervous system to execute nematode Caenorhabditis elegans. Genetic screens for animals and coordinate appropriate protective behaviors. They are often defective in touch sensation have revealed critical roles for polymodal neurons responding to multiple types of stimulation genes encoding TRP channels and DEG/ENaCs in behavioral including extreme temperatures, intense force, acid, and responses to mechanical inputs. The key insights derived from noxious chemicals. Other somatosensory neurons respond to genetic approaches have been reviewed elsewhere (Arnado´ ttir less intense stimulation and detect either temperature changes and Chalfie, 2010; Ernstrom and Chalfie, 2002). We review or mechanical stimulation, but not both. These cells provide data demonstrating that TRP channels and DEG/ENaC channels information about warmth, cooling, or the shape and texture of are widely distributed in the sensory neurons of vertebrates and objects. invertebrates and examine the idea that these channels have conserved, but distinct functions. We rely on investigations of Theater of Sensation somatosensory mechanoreceptors in nematodes, flies, and The skin is our largest sensory surface, extending nearly two mice, but recognize that on-going investigations in humans square meters in an average human. Mechanoreceptor neurons and other animals have the potential to deepen and expand are principal actors in this theater. They are responsible not only understanding of how mechanoreceptors function. for detecting mechanical cues, but also for encoding and trans- mitting all relevant information to the central nervous system. Sensing with Ion Channels Their performance is shaped by ion channels that include, but For several decades, attention has focused on the idea that are not limited to, sensory transduction channels. Agents that mechano-electrical transduction (MeT) channels are formed by Neuron 74, May 24, 2012 ª2012 Elsevier Inc. 609 Neuron Review assemble into homomeric or heteromeric ion channels (Venkata- chalam and Montell, 2007). Recently, two additional classes of membrane proteins (Piezo and TMC) have been linked to mecha- notransduction (Coste et al., 2010; Coste et al., 2012; Kawa- shima et al., 2011; Kim et al., 2012). Both TRPs and DEG/ENaCs are broadly expressed in somato- sensory neurons. Several mechanoreceptor neurons are known to coexpress multiple TRPs and multiple DEG/ENaC channels. Figure 2 aggregates evidence that these channels are coex- pressed in mechanoreceptor neurons from the growing but essentially independent literatures on TRP and DEG/ENaC chan- nels expression and function. Excluding reviews, PubMed listed 1,687 entries for DEG/ENaCs, 2,341 for TRP channels, and only 15 entries for both ion channel families on April 15, 2012 (search conducted with the following search terms: ‘‘TRP channels,’’ ‘‘ENaC OR ASIC OR degenerin,’’ and the union of both terms). Here, we focus on two invertebrates, Caenorhabditis elegans nematodes and Drosophila melanogaster fruitflies, and one mammal, the laboratory mouse. Despite the fact that members of these gene families are coexpressed, the function of individual TRP and DEG/ENaC channels is often explored subunit by subunit. But, genetic redundancy within each ion channel family and the potential for functional redundancy between the two Figure 1. Topology and Stoichiometry of Proteins Proposed to Form families limits insight derived from this approach. Additional MeT Channels in Animals The TRP channel genes are conserved in eukaryotes and encode proteins complications include alteration of channel function by their predicted to have six transmembrane domains and assemble into tetrameric association with heteromeric channel complexes and through ion channels. Many TRPs have ankyrin repeats in their intracellular amino alternative splicing of ion channel genes. terminal; some have more than ten such repeats (Venkatachalam and Montell, 2007). The DEG/ENaC genes are absent from plants, yeast, and other microbes, but conserved in animals (Goodman and Schwarz, 2003). They Stagecraft for Sensory Biology encode proteins with two transmembrane domains and a large extracellular A fundamental block to progress in understanding how mecha- domain. Three DEG/ENaC proteins assemble to form an ion channel. Both noreceptor neurons function is that studying stimulus-initiated TRP and DEG/ENaC proteins can form homomeric and heteromeric channels, increasing the potential for channel diversity. Recently, two addi- behavior, action potential generation, or intracellular calcium tional classes of membrane proteins (Piezo and TMC) have been linked to dynamics does not allow researchers to separate the initial step mechanotransduction in mammals (Coste et al., 2010; Kawashima et al., 2011) of mechanotransduction from amplification, gain control, and and Drosophila fruitflies (Kim et al., 2012). Piezo is sufficient to produce stretch activated channels in heterologous cells (Coste et al., 2010, 2012; Bae et al., transmission. Behavior, spikes, and calcium dynamics depend 2011) and purified Piezo forms a channel in lipid bilayers (Coste et al., 2012). on the action of all of the ion channels expressed by sensory TMC1 and TMC2 are required for mechanotransduction by sound- and neurons. These channels are interconnected in feedback loops vibration-sensing hair cells in mice (Kawashima et al., 2011). Both Piezo and regulated by a common control variable—membrane potential. TMC have homologs in invertebrates; a C. elegans TMC homolog is expressed in the multidendritic PVD nociceptors. The predicted topology and stoichi- The voltage-clamp uncouples such feedback loops by holding ometry of Piezo and TMC await further experimental confirmation. membrane potential constant and allows researchers to examine transduction independently of amplification, gain control, and proteins enriched in mechanoreceptor neurons and required for spike generation. Within this heuristic, deleting molecules their function. Figure 1 summarizes current knowledge about needed for the formation or function of MeT channels should elim- proteins proposed to
Load more

Recommended publications
  • On the Existence of Mechanoreceptors Within the Neurovascular Unit of the Rodent and Rabbit Brain
    bioRxiv preprint doi: https://doi.org/10.1101/480921; this version posted November 28, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. On the existence of mechanoreceptors within the neurovascular unit of the rodent and rabbit brain Jorge Larriva-Sahd, Martha León-Olea (*), Víctor Vargas-Barroso (**), Alfredo Varela-Echavarría and Luis Concha Departments of Developmental Biology and Physiology, Instituto de Neurobiología. Campus Juriquilla. Universidad Nacional Autónoma de México. Boulevard Universitario 3001, Juriquilla, Querétaro, CP 76230, México. (*) Department of Functional Neuromorphology, Instituto Mexicano de Psiquiatría “Ramón de la Fuente Muñiz” Av México Xochimilco 101, Delegación Tlalpan CP14370, México DF, México. (**) Present address: Institute of Science and Technology Austria (IST), Am Campus 1, 3400, Klosterneuburg, Austria.Correspondence: Correspondence: Jorge Larriva-Sahd e-mail: [email protected] Telephone: 5256-234030 Orcid ID: 0000-0002-7254-0773 bioRxiv preprint doi: https://doi.org/10.1101/480921; this version posted November 28, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. Abstract. We describe a set of perivascular interneurons (PINs) originating a series of fibro-vesicular complexes (FVCs) throughout the gray matter of the adult rabbit and rat brain. PINs-FVCs are ubiquitous throughout the brain vasculature as defined in Golgi-impregnated specimens.
    [Show full text]
  • Chemoreception
    Senses 5 SENSES live version • discussion • edit lesson • comment • report an error enses are the physiological methods of perception. The senses and their operation, classification, Sand theory are overlapping topics studied by a variety of fields. Sense is a faculty by which outside stimuli are perceived. We experience reality through our senses. A sense is a faculty by which outside stimuli are perceived. Many neurologists disagree about how many senses there actually are due to a broad interpretation of the definition of a sense. Our senses are split into two different groups. Our Exteroceptors detect stimulation from the outsides of our body. For example smell,taste,and equilibrium. The Interoceptors receive stimulation from the inside of our bodies. For instance, blood pressure dropping, changes in the gluclose and Ph levels. Children are generally taught that there are five senses (sight, hearing, touch, smell, taste). However, it is generally agreed that there are at least seven different senses in humans, and a minimum of two more observed in other organisms. Sense can also differ from one person to the next. Take taste for an example, what may taste great to me will taste awful to someone else. This all has to do with how our brains interpret the stimuli that is given. Chemoreception The senses of Gustation (taste) and Olfaction (smell) fall under the category of Chemoreception. Specialized cells act as receptors for certain chemical compounds. As these compounds react with the receptors, an impulse is sent to the brain and is registered as a certain taste or smell. Gustation and Olfaction are chemical senses because the receptors they contain are sensitive to the molecules in the food we eat, along with the air we breath.
    [Show full text]
  • The Roles and Functions of Cutaneous Mechanoreceptors Kenneth O Johnson
    455 The roles and functions of cutaneous mechanoreceptors Kenneth O Johnson Combined psychophysical and neurophysiological research has nerve ending that is sensitive to deformation in the resulted in a relatively complete picture of the neural mechanisms nanometer range. The layers function as a series of of tactile perception. The results support the idea that each of the mechanical filters to protect the extremely sensitive recep- four mechanoreceptive afferent systems innervating the hand tor from the very large, low-frequency stresses and strains serves a distinctly different perceptual function, and that tactile of ordinary manual labor. The Ruffini corpuscle, which is perception can be understood as the sum of these functions. located in the connective tissue of the dermis, is a rela- Furthermore, the receptors in each of those systems seem to be tively large spindle shaped structure tied into the local specialized for their assigned perceptual function. collagen matrix. It is, in this way, similar to the Golgi ten- don organ in muscle. Its association with connective tissue Addresses makes it selectively sensitive to skin stretch. Each of these Zanvyl Krieger Mind/Brain Institute, 338 Krieger Hall, receptor types and its role in perception is discussed below. The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218-2689, USA; e-mail: [email protected] During three decades of neurophysiological and combined Current Opinion in Neurobiology 2001, 11:455–461 psychophysical and neurophysiological studies, evidence has accumulated that links each of these afferent types to 0959-4388/01/$ — see front matter © 2001 Elsevier Science Ltd. All rights reserved. a distinctly different perceptual function and, furthermore, that shows that the receptors innervated by these afferents Abbreviations are specialized for their assigned functions.
    [Show full text]
  • Sensory Receptors
    Laboratory Worksheet Exercise: Sensory Receptors Sense Organs - Sensory Receptors A sensory receptor is a specialized ending of a sensory neuron that detects a specific stimulus. Receptors can range from simple nerve endings of a sensory neuron (e.g., pain, touch), to a complex combination of nervous, epithelial, connective and muscular tissue (e.g., the eyes). Axon Synaptic info. Sensory end bulbs Receptors Figure 1. Diagram of a sensory neuron with sensory information being detected by sensory receptors located at the incoming end of the neuron. This information travels along the axon and delivers its signal to the central nervous system (CNS) via the synaptic end bulbs with the release of neurotransmitters. The function of a sensory receptor is to act as a transducer. Transducers convert one form of energy into another. In the human body, sensory receptors convert stimulus energy into electrical impulses called action potentials. The frequency and duration of action potential firing gives meaning to the information coming in from a specific receptor. The nervous system helps to maintain homeostasis in the body by monitoring the internal and external environments of the body using receptors to achieve this. Sensations are things in our environment that we detect with our 5 senses. The 5 basic senses are: Sight Hearing Touch Taste Smell An adequate stimulus is a particular form of energy to which a receptor is most responsive. For example, thermoreceptors are more sensitive to temperature than to pressure. The threshold of a receptor is the minimum stimulus required to activate that receptor. Information about Receptor Transmission Sensory receptors transmit four kinds of information - modality, location, intensity and duration.
    [Show full text]
  • The Effect of Carotid Chemoreceptor Inhibition on Exercise Tolerance in Chronic Obstructive Pulmonary Disease: a Randomized-Controlled Crossover Trial
    Respiratory Medicine 160 (2019) 105815 Contents lists available at ScienceDirect Respiratory Medicine journal homepage: http://www.elsevier.com/locate/rmed The effect of carotid chemoreceptor inhibition on exercise tolerance in chronic obstructive pulmonary disease: A randomized-controlled crossover trial a,b � a,c a a Devin B. Phillips , Sophie E. Collins , Tracey L. Bryan , Eric Y.L. Wong , M. Sean McMurtry d, Mohit Bhutani a, Michael K. Stickland a,e,* a Division of Pulmonary Medicine, Faculty of Medicine and Dentistry, University of Alberta, Canada b Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Canada c Faculty of Rehabilitation Medicine, University of Alberta, Canada d Division of Cardiology, Faculty of Medicine and Dentistry, University of Alberta, Canada e G.F. MacDonald Centre for Lung Health, Covenant Health, Edmonton, Alberta, Canada ARTICLE INFO ABSTRACT Keywords: Background: Patients with chronic obstructive pulmonary disease (COPD) have an exaggerated ventilatory COPD response to exercise, contributing to exertional dyspnea and exercise intolerance. We recently demonstrated Exercise tolerance enhanced activity and sensitivity of the carotid chemoreceptor (CC) in COPD which may alter ventilatory and Carotid chemoreceptor cardiovascular regulation and negatively affect exercise tolerance. We sought to determine whether CC inhibi­ Dyspnea tion improves ventilatory and cardiovascular regulation, dyspnea and exercise tolerance in COPD. Methods: Twelve mild-moderate COPD patients (FEV1 83 � 15 %predicted) and twelve age- and sex-matched healthy controls completed two time-to-symptom limitation (TLIM) constant load exercise tests at 75% peak À À power output with either intravenous saline or low-dose dopamine (2 μg⋅kg 1⋅min 1, order randomized) to inhibit the CC.
    [Show full text]
  • Visions & Reflections on the Origin of Smell: Odorant Receptors in Insects
    Cell. Mol. Life Sci. 63 (2006) 1579–1585 1420-682X/06/141579-7 DOI 10.1007/s00018-006-6130-7 Cellular and Molecular Life Sciences © Birkhäuser Verlag, Basel, 2006 Visions & Reflections On the ORigin of smell: odorant receptors in insects R. Benton Laboratory of Neurogenetics and Behavior, The Rockefeller University, 1230 York Avenue, Box 63, New York, New York 10021 (USA), Fax: +1 212 327 7238, e-mail: [email protected] Received 23 March 2006; accepted 28 April 2006 Online First 19 June 2006 Abstract. Olfaction, the sense of smell, depends on large, suggested that odours are perceived by a conserved mecha- divergent families of odorant receptors that detect odour nism. Here I review recent revelations of significant struc- stimuli in the nose and transform them into patterns of neu- tural and functional differences between the Drosophila ronal activity that are recognised in the brain. The olfactory and mammalian odorant receptor proteins and discuss the circuits in mammals and insects display striking similarities implications for our understanding of the evolutionary and in their sensory physiology and neuroanatomy, which has molecular biology of the insect odorant receptors. Keywords. Olfaction, odorant receptor, signal transduction, GPCR, neuron, insect, mammal, evolution. Olfaction: the basics characterised by the presence of seven membrane-span- ning segments with an extracellular N terminus. OR pro- Olfaction is used by most animals to extract vital infor- teins are exposed to odours on the ciliated endings of olf- mation from volatile chemicals in the environment, such actory sensory neuron (OSN) dendrites in the olfactory as the presence of food or predators.
    [Show full text]
  • The Aer Protein and the Serine Chemoreceptor Tsr Independently
    Proc. Natl. Acad. Sci. USA Vol. 94, pp. 10541–10546, September 1997 Biochemistry The Aer protein and the serine chemoreceptor Tsr independently sense intracellular energy levels and transduce oxygen, redox, and energy signals for Escherichia coli behavior (signal transductionybacterial chemotaxisyaerotaxis) ANURADHA REBBAPRAGADA*, MARK S. JOHNSON*, GORDON P. HARDING*, ANTHONY J. ZUCCARELLI*†, HANSEL M. FLETCHER*, IGOR B. ZHULIN*, AND BARRY L. TAYLOR*†‡ *Department of Microbiology and Molecular Genetics and †Center for Molecular Biology and Gene Therapy, School of Medicine, Loma Linda University, Loma Linda, CA 92350 Edited by Daniel E. Koshland, Jr., University of California, Berkeley, CA, and approved July 17, 1997 (received for review May 6, 1997) ABSTRACT We identified a protein, Aer, as a signal conformational change in the signaling domain that increases transducer that senses intracellular energy levels rather than the rate of CheA autophosphorylation. The phosphoryl resi- the external environment and that transduces signals for due from CheA is transferred to CheY, which, in its phos- aerotaxis (taxis to oxygen) and other energy-dependent be- phorylated state, binds to a switch on the flagellar motors and havioral responses in Escherichia coli. Domains in Aer are signals a reversal of the direction of rotation of the flagella. similar to the signaling domain in chemotaxis receptors and Evidence that CheA, CheW, and CheY are also part of the the putative oxygen-sensing domain of some transcriptional aerotaxis response (12) led us to propose that the aerotaxis activators. A putative FAD-binding site in the N-terminal transducer would have (i) a C-terminal domain homologous to domain of Aer shares a consensus sequence with the NifL, Bat, the chemoreceptor signaling domain that modulates CheA and Wc-1 signal-transducing proteins that regulate gene autophosphorylation and (ii) a domain that senses oxygen.
    [Show full text]
  • 36 | Sensory Systems 1109 36 | SENSORY SYSTEMS
    Chapter 36 | Sensory Systems 1109 36 | SENSORY SYSTEMS Figure 36.1 This shark uses its senses of sight, vibration (lateral-line system), and smell to hunt, but it also relies on its ability to sense the electric fields of prey, a sense not present in most land animals. (credit: modification of work by Hermanus Backpackers Hostel, South Africa) Chapter Outline 36.1: Sensory Processes 36.2: Somatosensation 36.3: Taste and Smell 36.4: Hearing and Vestibular Sensation 36.5: Vision Introduction In more advanced animals, the senses are constantly at work, making the animal aware of stimuli—such as light, or sound, or the presence of a chemical substance in the external environment—and monitoring information about the organism’s internal environment. All bilaterally symmetric animals have a sensory system, and the development of any species’ sensory system has been driven by natural selection; thus, sensory systems differ among species according to the demands of their environments. The shark, unlike most fish predators, is electrosensitive—that is, sensitive to electrical fields produced by other animals in its environment. While it is helpful to this underwater predator, electrosensitivity is a sense not found in most land animals. 36.1 | Sensory Processes By the end of this section, you will be able to do the following: • Identify the general and special senses in humans • Describe three important steps in sensory perception • Explain the concept of just-noticeable difference in sensory perception Senses provide information about the body and its environment. Humans have five special senses: olfaction (smell), gustation (taste), equilibrium (balance and body position), vision, and hearing.
    [Show full text]
  • Mechanoreceptor Synapses in the Brainstem Shape the Central Representation of Touch
    bioRxiv preprint doi: https://doi.org/10.1101/2021.02.02.429463; this version posted February 3, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Mechanoreceptor synapses in the brainstem shape the central representation of touch Brendan P. Lehnert1,2#, Celine Santiago1,2#, Erica L. Huey1,2, Alan J. Emanuel1,2, Sophia Renauld1,2, Nusrat Africawala1,2, Ilayda Alkislar1,2, Yang Zheng1,2, Ling Bai1,2, Charalampia Koutsioumpa1,2, Jennifer T. Hong1,2, Alexandra R. Magee1,2, Christopher D. Harvey1, David D. Ginty1,2* 1Department of Neurobiology, 2Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 # Co-first author. *Correspondence: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2021.02.02.429463; this version posted February 3, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract Mammals use glabrous (hairless) skin of their hands and feet to navigate and manipulate their environment. Cortical maps of the body surface across species contain disproportionately large numbers of neurons dedicated to glabrous skin sensation, potentially reflecting a higher density of mechanoreceptors that innervate these skin regions. Here, we find that disproportionate representation of glabrous skin emerges over postnatal development at the first synapse between peripheral mechanoreceptors and their central targets in the brainstem.
    [Show full text]
  • Chemical and Electric Transmission in the Carotid Body Chemoreceptor Complex
    EYZAGUIRRE Biol Res 38, 2005, 341-345 341 Biol Res 38: 341-345, 2005 BR Chemical and electric transmission in the carotid body chemoreceptor complex CARLOS EYZAGUIRRE Department of Physiology, University of Utah School of Medicine, Research Park, Salt Lake City, Utah, USA ABSTRACT Carotid body chemoreceptors are complex secondary receptors. There are chemical and electric connections between glomus cells (GC/GC) and between glomus cells and carotid nerve endings (GC/NE). Chemical secretion of glomus cells is accompanied by GC/GC uncoupling. Chemical GC/NE transmission is facilitated by concomitant electric coupling. Chronic hypoxia reduces GC/GC coupling but increases G/NE coupling. Therefore, carotid body chemoreceptors use chemical and electric transmission mechanisms to trigger and change the sensory discharge in the carotid nerve. Key terms: carotid body, chemosensory activity, glomus cells. The subject of this short review is highly Years later, with the advent of the appropriate since we are honoring Prof. electron microscope, it was found that the Patricio Zapata who has been a pioneer in glomus cells were connected synaptically this field and has done extensive to the carotid nerve endings (for refs. see pharmacological studies on chemical Mc Donald, 1981; Verna, 1997). Then, the synaptic transmission in the carotid body. problems started because of the location of Dr. Zapata is an excellent scientist and clear core synaptic vesicles. At the time, teacher, and I dearly value him as a friend these structures were supposed to be a and colleague. marker of pre-synaptic elements, and in the carotid body, they appeared some times in the glomus cells but very often in NATURE OF THE CAROTID BODY INNERVATION carotid nerve endings.
    [Show full text]
  • A Computational Model for Pain Processing in the Dorsal Horn Following Axonal Damage to Receptor Fibers
    brain sciences Article A Computational Model for Pain Processing in the Dorsal Horn Following Axonal Damage to Receptor Fibers Jennifer Crodelle 1,*,† and Pedro D. Maia 2,† 1 Department of Mathematics, Middlebury College, Middlebury, VT 05753, USA 2 Department of Mathematics, University of Texas at Arlington, Arlington, TX 76019, USA; [email protected] * Correspondence: [email protected] † Both authors contributed equally to this work. Abstract: Computational modeling of the neural activity in the human spinal cord may help elucidate the underlying mechanisms involved in the complex processing of painful stimuli. In this study, we use a biologically-plausible model of the dorsal horn circuitry as a platform to simulate pain processing under healthy and pathological conditions. Specifically, we distort signals in the receptor fibers akin to what is observed in axonal damage and monitor the corresponding changes in five quantitative markers associated with the pain response. Axonal damage may lead to spike-train delays, evoked potentials, an increase in the refractoriness of the system, and intermittent blockage of spikes. We demonstrate how such effects applied to mechanoreceptor and nociceptor fibers in the pain processing circuit can give rise to dramatically distinct responses at the network/population level. The computational modeling of damaged neuronal assemblies may help unravel the myriad of responses observed in painful neuropathies and improve diagnostics and treatment protocols. Citation: Crodelle, J.; Maia, P.D. A Computational Model for Pain Keywords: pain processing; dorsal horn; neuronal dynamics; computational model; axonal damage; Processing in the Dorsal Horn painful neuropathies Following Axonal Damage to Receptor Fibers. Brain Sci. 2021, 11, 505.
    [Show full text]
  • Quantification of Oral Roughness Perception and Comparison with Mechanism of Astringency Perception
    Quantification of oral roughness perception and comparison with mechanism of astringency perception THESIS Presented in Partial Fulfillment of the Requirements for the Degree Master of Science in the Graduate School of The Ohio State University By Brianne Linne Graduate Program in Food Science and Technology The Ohio State University 2016 Master's Examination Committee: Dr. Christopher Simons, Advisor Dr. Monica Giusti Dr. Lynn Knipe Copyrighted by Brianne Linne 2016 Abstract Texture plays a vital role in food preference and acceptance, but oral tactile texture perception is incompletely understood. A wide body of information currently exists on tactile perception of the hands and fingertips. Tactile perception in the hands and finger tips is mediated by nerve fibers, both slowly adapting and fast adapting, which terminate in four different types of mechanoreceptors; Merkel cells, Meissner corpuscles, Ruffini endings, and Pacinian corpuscles. These same mechanoreceptors are present in the tongue, with the exception of Pacinian corpuscles. It therefore, should be possible to use the knowledge of tactile perception in the skin and translate this to a better understanding of tactile perception of the tongue and other oral surfaces. In this study, individual sensitivities to oral tactile roughness are quantified, and the factors that may drive potential differences in sensitivity are examined. Additionally, a relationship between astringency and oral mechanisms of tactile roughness perception is investigated. If the sensation of astringency is purely the result of friction between oral surfaces due to decreased lubricity following astringent- protein complex precipitation, then an individual’s sensitivity to tactile roughness, perceived by activation of oral mechanoreceptors, should be indicative of how sensitive they are to astringent stimuli.
    [Show full text]